Friday, Oct. 14, 2016: The National Institutes of Health National Heart, Lung and Blood Institute (NIH NHLBI) has awarded a $2.4 million grant over four years to Cleveland Clinic cancer researchers Jaroslaw Maciejewski, M.D., and Richard Padgett, Ph.D., to test the hypothesis that alterations in the pattern of splicing of target genes play a major role in the establishment or progression of myelodysplastic syndromes (MDS).
Through this work, the researchers aim to further clarify the role of spliceosomal factor mutations and deletions, commonly identified in myeloid malignancies, in the pathogenesis of these diseases through the identification of their effects on mRNA splicing in vivo and in vitro.
"Both clinical and specialized basic science expertise are required for the successful completion of the studies," said Dr. Maciejewski, who chairs the Department of Translational Hematology and Oncology Research in Cleveland Clinic's Taussig Cancer Institute and Lerner Research Institute. "In collaboration with Dr. Padgett's lab, we are eager to leverage this R01 grant to better understand spliceosomal defects in MDS."
Dr. Maciejewski's laboratory was among the first to report mutations in components of the spliceosomal machinery in myeloid malignancies, including MDS and acute myeloid leukemia (AML). Dr. Maciejewski's group has also extensively studied mutations in other pathways in MDS and AML. His clinical Bone Marrow Failure Program accrues around 120 new cases of MDS per year, which can be genotyped and provide a clinical substrate for this new research.
Dr. Padgett's laboratory in the Lerner Research Institute specializes in the investigation of spliceosomal function and has made key contributions to the understanding of spliceosomal biology. His and Dr. Maciejewski's laboratories have combined to publish studies on several spliceosomal proteins mutated in MDS and AML.
The NIH defines MDS as a group of cancers that occur when not enough mature, healthy blood cells are formed in the bone marrow. Approximately 10,000 Americans are diagnosed annually.
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About the Lerner Research Institute
The Lerner Research Institute (LRI) is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. In 2015, LRI researchers published nearly 600 articles in high-impact biomedical journals (top 10% of all biomedical journals). LRI's total annual research expenditure was $251 million in 2015 (with $104 million in competitive federal funding). Approximately 1,200 people (including approximately 150 principal investigators, 200 research fellows, and about 100 graduate students) in 12 departments work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious diseases. The LRI has more than 700,000 square feet of lab, office, and scientific core services space. LRI faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University - training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The LRI is a significant source of commercial property, generating 54 invention disclosures, 14 licenses, and 76 patents in 2015.
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